PMID: 8604008Mar 1, 1996Paper

Myocardial protection by N,N,N-trimethylsphingosine in ischemia reperfusion injury is mediated by inhibition of P-selectin

Journal of Leukocyte Biology
R ScaliaA M Lefer

Abstract

Polymorphonuclear leukocytes (PMNs) play an important role in myocardial ischemia/reperfusion (MI/R) injury. We examined the cardioprotective effects of N,N,N-trimethylsphingosine (TMS) in a murine model of MI (20 min) and R (24 h) injury in vivo, focusing on leukocyte-endothelial interactions. TMS is a synthetic N-methylated sphingosine derivative that has protein kinase C inhibitory activity and has been shown to prevent leukocyte activation. TMS (18 microgram/kg), administered intravenously 1 min prior to reperfusion, significantly attenuated myocardial necrotic injury assessed by myocardial creatine kinase loss compared with MI/R rats receiving only vehicle (P<0.001). Cardiac myeloperoxidase activity, an index of PMN accumulation in the ischemic myocardium, was also significantly attenuated by TMS compared with rats receiving vehicle (P<0.001). We further examined whether TMS can attenuate leukocyte-endothelial interaction by intravital microscopy. TMS significantly attenuated NG-nitro-L-arginine-methyl ester (L-NAME)-stimulated PMN rolling and adherence to the rat microvascular endothelium. This action of TMS appears to be mediated by reduction of P-selectin expression because immunohistochemical analysis demonstrated that...Continue Reading

Citations

Jul 17, 2007·American Journal of Physiology. Heart and Circulatory Physiology·Susheel GundewarDavid J Lefer
May 10, 2005·The Journal of Pharmacology and Experimental Therapeutics·Didi OmiyiLindon H Young
Apr 9, 2004·Journal of Cardiovascular Pharmacology·Ellen E PetermanLindon H Young
Jan 26, 2007·ChemMedChem·Antonio DelgadoGemma Fabriás
Oct 28, 2005·Cardiovascular Drug Reviews·Lindon H YoungMargaret T Weis
Mar 30, 2000·Autoimmunity·M B Kahaleh, E C LeRoy
Dec 29, 1998·Transplantation Proceedings·H Beekhuizen, J S van de Gevel
Oct 12, 2007·Biochimica Et Biophysica Acta·Susheel Gundewar, David J Lefer
Dec 17, 2008·Current Opinion in Pharmacology·Simon KennedySusan Pyne

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